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Absence of Mucosal Immunity in the Human Upper Respiratory Tract to the Commensal Bacteria Neisseria lactamica but Not Pathogenic Neisseria meningitidis during the Peak Age of Nasopharyngeal Carriage¹

Andrew T. Vaughan^2,*, Andrew Gorringe, Victoria Davenport, Neil A. Williams^* and Robert S. Heyderman^*,

^* Department of Cellular and Molecular Medicine, School of Medical Science, University of Bristol, Bristol, United Kingdom; Health Protection Agency, Center for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom; Center for Research in Biomedicine, Faculty of Applied Sciences, Frenchay Campus, University of the West of England, Bristol, United Kingdom; and Malawi-Liverpool-Wellcome Trust, Clinical Research Programme, Chichiri, Blantyre, Malawi

The normal flora that colonizes the mucosal epithelia has evolved diverse strategies to evade, modulate, or suppress the immune system and avoid clearance. Neisseria lactamica and Neisseria meningitidis are closely related obligate inhabitants of the human upper respiratory tract. N. lactamica is a commensal but N. meningitidis is an opportunistic pathogen that occasionally causes invasive disease such as meningitis and septicemia. We demonstrate that unlike N. meningitidis, N. lactamica does not prime the development of mucosal T or B cell memory during the peak period of colonization. This cannot be explained by the induction of peripheral tolerance or regulatory CD4⁺CD25⁺ T cell activity. Instead, N. lactamica mediates a B cell-dependent mitogenic proliferative response that is absent to N. meningitidis. This mitogenic response is associated with the production of T cell-independent polyclonal IgM that we propose functions by shielding colonizing N. lactamica from the adaptive immune system, maintaining immunological ignorance in the host. We conclude that, in contrast to N. meningitidis, N. lactamica maintains a commensal relationship with the host in the absence of an adaptive immune response. This may prolong the period of susceptibility to colonization by both pathogenic and nonpathogenic Neisseria species.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by the Health Protection Agency, U.K.

² Address correspondence and reprint requests to Dr. Andrew Vaughan, Department of Cellular and Molecular Medicine, School of Medical Science, University Walk, Bristol, United Kingdom. E-mail address: andrew.vaughan{at}emory.edu

³ Abbreviations used in this paper: Treg, regulatory T cell; URT, upper respiratory tract; Nm, Neisseria meningitidis; OMV, outer membrane vesicle; PT, palatine tonsil; Nl, Neisseria lactamica; LOS, lipooligosaccharide; flu, trivalent inactivated split-virion influenza vaccine; SAC, Staphylococcus aureus cowan I strain; ODN, oligodeoxynucleotide; TMNC, tonsillar mononuclear cell; KLH, keyhole limpet hemocyanin; ASC, Ab secreting cell; AP, alkaline phosphatase.